AZ gets early FDA green light for Imbruvica challenger

AstraZeneca claimed its first regulatory approval for BTK inhibitor acalabrutinib in the US, with the FDA clearing the drug for second-line therapy for adults with mantel cell lymphoma.

The new product - which will be sold in the US as Calquence - has been approved much earlier than expected, bringing forward a marketing battle with Johnson/AbbVie's big-selling Imbruvica (ibrutinib) which is already approved for MCL as well as other blood cancers. The FDA has previously awarded acalabrutinib breakthrough and priority review status and had been scheduled to compete its review in the first quarter of next year.

The new product will launch with a list price of around $14,260 per month or $171,108 per year - which is roughly in line with Imbruvica - and according to analysts at Leerink seems to be better tolerated and may have better efficacy based on an admittedly limited phase II data set.

That could help it mount a challenge to Imbruvica, although it’s a tough act to follow, with AbbVie and J&J’s drug having already passed $2.2bn in sales last year and predicted to reach $7.5bn by 2022, according to EvaluatePharma.

AZ thinks that Calquence has a best-in-class profile that could help catapult the drug to $5bn in peak sales, but analysts appear to be more cautious, with consensus estimates around the $1bn area in five years.

That would still make it a key part of AZ’s oncology renaissance, which is being spearheaded by PARP inhibitor Lynparza (olaparib), new-generation EGFR inhibitor Tagrisso (osimertinib) and PD-L1 inhibitor Imfinzi (durvalumab).

AZ chief executive Pascal Soriot described the approval as a “landmark moment” for the company, adding that Calquence will be the “cornerstone of our presence in oncology”.

The drug is being tested in additional indications already held by Imbruvica - including the larger chronic lymphocytic leukaemia (CLL) market and Waldenström’s macroglobulinemia - and AZ is also running a head-to-head comparison of the two drugs in CLL. Data from most of those studies is due in 2019.

AZ picked up rights to acalabrutinib when it took control of Acerta Pharma in 2015, buying a majority stake in the Dutch biotech in a deal valued at up to $7bn, and there is now speculation that it may now buy the remaining 45% of the firm.

According to the FDA, MCL is a rare and fast-growing type of non-Hodgkin’s lymphoma (NHL) and accounts for 3-10% of all NHL cases in the US. It is a “particularly aggressive cancer”, said the agency’s acting director of the Office of Haematology and Oncology Products Richard Pazdur, and “provides a new treatment option that has shown high rates of response for some patients in initial studies”.